Cyclosporine Microemulsion Research Articles

Rectal carcinoma 27 years' postkidney transplant in a chronic hepatitis B patient - A case report

Here, we report a 72-year-old male with HBsAg-positive status who had a live sibling kidney transplant 27 years ago. He was on minimal maintenance immunosuppressive therapy with prednisolone and microemulsion cyclosporine. He presented with vague abdominal symptoms and was diagnosed to have moderately differentiated adenocarcinoma of the rectum, which was treated by low anterior resection with loop ileostomy and is currently undergoing radiotherapy.

Randomized trial of 3 maintenance regimens (TAC/SRL vs. TAC/MMF vs. CSA/SRL) with low-dose corticosteroids in primary kidney transplantation: 18-year results.

A randomized trial of 150 primary kidney transplant recipients, initiated in May 2000, compared tacrolimus (TAC)/sirolimus (SRL) vs. TAC/mycophenolate mofetil (MMF) vs. cyclosporine microemulsion (CSA)/SRL (N=50/group). All patients received daclizumab induction and maintenance corticosteroids. With current median follow-up of 18years post-transplant, biopsy-proven acute rejection (BPAR) occurred less often in TAC/MMF (26% (13/50)), vs. the TAC/SRL (36% (18/50)) and CSA/SRL (34% (17/50)) arms combined (p=.23), with statistical significance favoring TAC/MMF (p=.05) after controlling for the multivariable (Cox model) effects of recipient age, recipient race/ethnicity, and donor age. First BPAR rate was clearly more favorable for TAC/MMF after stratifying patients by having 0-1 (N=72) vs. 2-3 (N=78) unfavorable baseline characteristics (recipient age <50years, African American or Hispanic recipient, and donor age ≥50years) (p=.02). Mean estimated glomerular filtration rate (eGFR), using the CKD-EPI formula, was consistently higher for TAC/MMF, particularly after controlling for the multivariable effect of donor age, throughout the first 96months post-transplant (p≤.008). These differences were translated into an observed more favorable graft failure due to immunologic cause (CAI/TG) rate for TAC/MMF (p=.06), although no significant differences in overall death-uncensored graft loss were observed. Previously reported significantly higher study drug discontinuation and requirement for antilipid therapy rates in the SRL-assigned arms were maintained over time. Overall, these results at 18years post-transplant more definitively show that TAC/MMF should be the gold standard for achieving optimal, long-term maintenance immunosuppression in kidney transplantation.

Comparison of Efficacy and Sensation of Instillation between 0.05% Cyclosporine Nanoemulsion and Microemulsion Type

Comparison of Efficacy and Sensation of Instillation between 0.05% Cyclosporine Nanoemulsion and Microemulsion Type

Kidney transplantation from an anti-hepatitis C virus antibody-positive donor into an anti-hepatitis C virus antibody-negative recipient: A case report

Patients who test positive for hepatitis C virus (HCV) antibody are not considered suitable living kidney donor candidates for HCV negative recipients. Here, we report a case of an HCV positive patient treated successfully with antiviral therapy, achieving sustained virologic response (SVR), who subsequently donated a kidney to an HCV negative recipient without viral transmission. This suggests that HCV positive patients who achieve SVR may safely donate kidneys.A 66-year-old male with end-stage renal disease had been on hemodialysis for 7 years. His 63-year-old wife was a candidate for living donation, but had a history of HCV infection. She had received interferon-beta treatment 12 years previously. After the treatment, SVR was achieved and her liver enzymes were normalized. The recipient received a preconditioning regimen comprising a single dose of rituximab combined with cyclosporine microemulsion and mycophenolate mofetil 2 weeks before the transplantation for the desensitization of anti-blood type antibody. The operation was performed with no adverse events. Protocol kidney biopsies at 3 and 12 months showed no signs of rejection. The recipient's liver function tests remained within the normal range, HCV antibody testing was negative, and HCV RNA was undetectable at the 1-year follow-up. At the time of this writing, the recipient is healthy with a serum creatinine level of 1.2mg/dL. Likewise, the donor is healthy with follow up indicating SVR, normal liver enzymes, and normal renal function.In conclusion, only in selected cases, HCV antibody positive donors may be taken into consideration as a kidney donor.

Weight-based dosing in medication use: what should we know?

BackgroundWeight-based dosing strategy is still challenging due to poor awareness and adherence. It is necessary to let clinicians know of the latest developments in this respect and the correct circumstances in which weight-based dosing is of clinical relevance.MethodsA literature search was conducted using PubMed.ResultsClinical indications, physiological factors, and types of medication may determine the applicability of weight-based dosing. In some cases, the weight effect may be minimal or the proper dosage can only be determined when weight is combined with other factors. Medications within similar therapeutic or structural class (eg, anticoagulants, antitumor necrosis factor medications, P2Y12-receptor antagonists, and anti-epidermal growth factor receptor antibodies) may exhibit differences in requirements on weight-based dosing. In some cases, weight-based dosing is superior to currently recommended fixed-dose regimen in adult patients (eg, hydrocortisone, vancomycin, linezolid, and aprotinin). On the contrary, fixed dosing is noninferior to or even better than currently recommended weight-based regimen in adult patients in some cases (eg, cyclosporine microemulsion, recombinant activated Factor VII, and epoetin α). Ideal body-weight-based dosing may be superior to the currently recommended total body-weight-based regimen (eg, atracurium and rocuronium). For dosing in pediatrics, whether weight-based dosing is better than body surface-area-based dosing is dependent on the particular medication (eg, methotrexate, prednisone, prednisolone, zidovudine, didanosine, growth hormone, and 13-cis-retinoic acid). Age-based dosing strategy is better than weight-based dosing in some cases (eg, intravenous busulfan and dalteparin). Dosing guided by pharmacogenetic testing did not show pharmacoeconomic advantage over weight-adjusted dosing of 6-mercaptopurine. The common viewpoint (ie, pediatric patients should be dosed on the basis of body weight) is not always correct. Effective weight-based dosing interventions include standardization of weight estimation, documentation and dosing determination, dosing chart, dosing protocol, order set, pharmacist participation, technological information, and educational measures.ConclusionAlthough dosing methods are specified in prescribing information for each drug and there are no principal pros and cons to be elaborated, this review of weight-based dosing strategy will enrich the knowledge of medication administration from the perspectives of safety, efficacy, and pharmacoeconomics, and will also provide research opportunities in clinical practice. Clinicians should be familiar with dosage and administration of the medication to be prescribed as well as the latest developments.

Therapeutic drug monitoring of cyclosporine microemulsion in patients with corticosteroid-resistant systemic lupus erythematosus

Objectives. We retrospectively examined how the cyclosporine-A (CSA) microemulsion administration mode affected blood CSA levels, as well as how the dose and blood levels of CSA affected its therapeutic effect against systemic lupus erythematosus (SLE).Methods. We calculated the area under the blood concentration time curve (AUC) of CSA in 16 patients with corticosteroid-resistant SLE, and analyzed its correlation with CSA levels at the blood sampling time points to investigate the optimum monitoring and dosing regimen.Results. The blood CSA level peaked at 2 h after administration (C2) in all patients. AUC0-6, which most markedly reflects the immunosuppressive effect, significantly correlated with C2 (R2 = 0.905), but not with the trough (C0). In concentration/dose ratio (C/D) of CSA, C2/D level was significantly higher when administered once daily before breakfast than when administered in the divided dose after meals (R2 = 0.355, P = 0.015), but not C0/D. During the 6-month follow-up, the CSA C2 tended to correlate with improvement in SLE disease activity index 2000 (R2 = 0.633, P = 0.067).Conclusions. The treatment with a single dose of CSA before breakfast, followed by monitoring of C2, may be useful for improving the therapeutic effect in patients with corticosteroid-resistant SLE.

アトピー性皮膚炎患者におけるシクロスポリン100 mg 1日1回内服療法の有効性の検討

アトピー性皮膚炎患者におけるシクロスポリン100 mg 1日1回内服療法の有効性の検討

Calcineurin Inhibitor (CI) Use Reduces the Risk of Donor-Specific Antibody (DSA) Development After Kidney and Kidney/pancreas Transplant.

Background. The number of available drugs for use in maintenance immunosuppression regimens makes it possible to employ various combinations to avoid undesirable side effects or toxicities. This study was performed to compare overt evidence of allosensitization post-transplant with the use of various immunosuppression drugs within the first year post-transplant. Methods. Between 1/1/2002 and 12/31/2012 2455 adult, ABO compatible, XM negative kidney and combined kidney/pancreas transplants were performed and in 1757 transplants donor specific antibodies (DSA) were obtained post-transplant for surveillance or as a cause of organ dysfunction. Maintenance immunosuppression drugs consisted of microemulsion cyclosporine (CI), rapamune, and mycophenolic acid in various combinations without maintenance steroids. Exposure to each maintenance immunosuppression drug was determined at 1, 3, 6, and 12 months after transplant. Results. Of the 1756 transplants, 318 recipients (18.1%) developed at least 1 biopsy proven acute rejection (AR) episode. AR was associated with a high incidence of DSA detection, 49.7% (150/318) versus 12.4% (178/1439) without AR (HR = 6.6, CI 5.0 - 8.6, p<0.001). When analyzing maintenance immunosuppression drugs, only lack of CI exposure at 1, 3, 6 or 12 months post-transplant correlated with a significantly higher incidence of DSA development (p<0.001 for all time points). But lack of CI exposure also correlated with AR development (about 24% versus 14%, p<0.001 for all time points), obscuring the significance of CI exposure. However, when analyzing only transplants without AR, lack of CI exposure at 1, 3, 6 or 12 months post-transplant still correlated with a significantly higher incidence of DSA development (17-18% versus 10-11%, p<0.005 for all time points). When controlling for recipient age, African-American ethnicity, primary versus retransplantation, and living versus deceased donor in the 1438 transplants without AR, the increased risk of developing detectable DSA ranged from 59% to 77% when recipients were not exposed to a CI at 1, 3, 6 or 12 months after transplant. Conclusion. Use of a calcineurin inhibitor during the first post-transplant year reduces the risk of developing DSA after kidney or kidney/pancreas transplantation by decreasing the incidence of AR, and DSA in the absence of AR.

Therapeutic monitoring of pediatric renal transplant patients with conversion to generic cyclosporin.

Cyclosporin is a calcineurin inhibitor widely used in renal transplant patients to prevent organ rejection. Several position papers have been published but no reports on the practical experience in pediatric patients undergoing conversion between cyclosporin innovator and generic products are available. To evaluate the pharmacokinetics and safety as part of therapeutic monitoring of cyclosporin in renal transplant pediatric patients who switch from the innovator to the generic formulation in Argentina. Hospital de Pediatría JP Garrahan, Buenos Aires, Argentina. Stable pediatric renal transplant patients (6 months post-transplant) switched from the innovator to the generic formulation of cyclosporin microemulsion capsule. Cyclosporin pharmacokinetic parameters were obtained while taking the innovator and after starting with the generic formulation. Blood samples were drawn before and 1, 2, and 3 h after drug administration and subsequently quantified. Pharmacokinetic parameters were obtained by means of a Bayesian approach. Cyclosporin pharmacokinetic parameters (area under the curve, AUC; Blood concentration after 2 h, C2), adverse events and graft rejection. A total of 12 patients were included. Median (range) age and time post-transplant were 10.7 years (6.5-17.7) and 8.3 years (3.4-14.0), respectively. Two patients or their parents did not consent to the switch. Median (range) dose normalized cyclosporin AUC and C2 were 1.15 (mg*h/L)/mg/kg (0.72-3.0) and 265.5 (ng/ml)/mg/kg (120.8-725.7), respectively, on the innovator therapy and 1.05 (mg*h/L)/mg/kg (0.54-2.22) and 317.1 (ng/ml)/mg/kg (116.7-564.7) for the generic drug after the switch. The median (range) percentage of change in the AUC and C2 when switching between formulations were 16.7 % (0.7-56.7) and 13.1 % (3.7-68.6), respectively. No significant changes in serum creatinine levels were registered when comparing before and after substitution of products. Adverse events (number of events) recorded 5 months before and after the switch included hirsutism (2), hypertension (2), and gingival hyperplasia (1). Conversion of cyclosporin from innovator brand to generic in pediatric renal transplant patients needs to be closely monitored.

Drug Interaction Between Oral Cyclosporine Modified and Iron.

To describe a recent case of suspected interaction between oral cyclosporine modified and iron. A 33-year-old man underwent urgent cardiac transplantation for refractory cardiogenic shock caused by acute myocarditis. The patient had persistently low levels of cyclosporine despite a dose increase of the drug after the change of administration route from intravenous to oral. Spacing the administration of cyclosporine modified from oral iron resolved the problem. This drug interaction was reported as "probable" as determined by a Drug Interaction Probability Scale score of 7. Using this scoring system, the patient experienced a probable drug interaction between cyclosporine and iron both administered orally, and we surmise that the mechanism is that iron physicochemically destabilizes the cyclosporine microemulsion when both are administered concurrently. This may be because of the interaction between cyclosporine microemulsion and iron because this cation can destabilize the immunosuppressant dosage form. Taking into account that joint administration of oral iron and cyclosporine modified can generate a physicochemical interaction that involves a decrease in the absorption of cyclosporine modified, we believe that it is necessary to recommend spacing administrations of both drugs as well as monitoring levels of cyclosporine in order to ensure optimal levels of immunosuppression.

Efficacious treatment of psoriasis with low‐dose and intermittent cyclosporin microemulsion therapy

Cyclosporin is used for moderate to severe psoriasis and improves not only the skin lesions but also quality of life of the patients. To improve its safe use, we evaluated a low-dose, intermittent regimen of cyclosporin in the treatment of psoriasis vulgaris. Seventy-three patients received approximately 2.5mg/kg per day of cyclosporin microemulsion twice daily before breakfast and dinner for 2-12weeks until 75% reduction was achieved in Psoriasis Area and Severity Index (PASI) score. When the skin lesions relapsed after cessation of cyclosporin and showed less than 50% reduction from baseline in PASI score, cyclosporin was restarted. This cessation and restart cycle was repeated if necessary. Treatment outcomes were assessed at 12, 48 and 96weeks after initiation of the therapy. The initial dose of cyclosporin was 2.32±0.27 (standard deviation [SD]) mg/kg per day. At baseline, the mean PASI score was 11.3±5.3 (SD). An average of 49.8±23.8 (SD) days of the therapy achieved PASI 75% reduction. In 20 of 73 patients, the second course of cyclosporin was required. The mean interval between the first and second course was 94days. An average of 60.8±26.9days was required to achieve PASI 75% reduction in the second course, which was not significantly longer than that in the first course. Only six patients required cyclosporin for 96weeks. The adverse effects included one case of hypertension. Our study suggests that low-dose, intermittent cyclosporin microemulsion is efficacious for the treatment of moderate to severe psoriasis.

Quality by Design Approach for Understanding the Critical Quality Attributes of Cyclosporine Ophthalmic Emulsion

Restasis is an ophthalmic cyclosporine emulsion used for the treatment of dry eye syndrome. There are no generic products for this product, probably because of the limitations on establishing in vivo bioequivalence methods and lack of alternative in vitro bioequivalence testing methods. The present investigation was carried out to understand and identify the appropriate in vitro methods that can discriminate the effect of formulation and process variables on critical quality attributes (CQA) of cyclosporine microemulsion formulations having the same qualitative (Q1) and quantitative (Q2) composition as that of Restasis. Quality by design (QbD) approach was used to understand the effect of formulation and process variables on critical quality attributes (CQA) of cyclosporine microemulsion. The formulation variables chosen were mixing order method, phase volume ratio, and pH adjustment method, while the process variables were temperature of primary and raw emulsion formation, microfluidizer pressure, and number of pressure cycles. The responses selected were particle size, turbidity, zeta potential, viscosity, osmolality, surface tension, contact angle, pH, and drug diffusion. The selected independent variables showed statistically significant (p < 0.05) effect on droplet size, zeta potential, viscosity, turbidity, and osmolality. However, the surface tension, contact angle, pH, and drug diffusion were not significantly affected by independent variables. In summary, in vitro methods can detect formulation and manufacturing changes and would thus be important for quality control or sameness of cyclosporine ophthalmic products.

Significance of combined cyclosporine−prednisolone therapy and cyclosporine blood concentration monitoring for idiopathic membranous nephropathy with steroid-resistant nephrotic syndrome: a randomized controlled multicenter trial

BackgroundCombined treatment with cyclosporine microemulsion preconcentrate (CyA MEPC) and steroids has been widely used for idiopathic membranous nephropathy (IMN) associated with steroid-resistant nephrotic syndrome (SRNS). Recent studies have shown that once-a-day and preprandial administration of CyA MEPC is more advantageous than the conventional twice-a-day administration in achieving the target blood CyA concentration at 2 h post dose (C2). We designed a randomized trial to compare these administrations.MethodsIMN patients with SRNS (age 16–75 years) were divided prospectively and randomly into 2 groups. In group 1 (n = 23), 2–3 mg/kg body weight (BW) CyA MEPC was given orally once a day before breakfast. In group 2 (n = 25), 1.5 mg/kg BW CyA MEPC was given twice a day before meals. CyA + prednisolone was continued for 48 weeks.ResultsGroup 1 showed a significantly higher cumulative complete remission (CR) rate (p = 0.0282), but not when incomplete remission 1 (ICR1; urine protein 0.3–1.0 g/day) was added (p = 0.314). Because a C2 of 600 ng/mL was determined as the best cut-off point, groups 1 and 2 were further divided into subgroups A (C2 ≥600 ng/mL) and B (C2 <600 ng/mL). Groups 1A and 2A revealed significantly higher cumulative remission (CR + ICR1) (p = 0.0069) and CR-alone (p = 0.0028) rates. On the other hand, 3 patients with high CyA levels (C2 >900 ng/mL) in Group 1A were withdrawn from the study because of complications.ConclusionCyA + prednisolone treatment is effective for IMN with associated SRNS at a C2 of ≥600 ng/mL. To achieve remission, preprandial once-a-day administration of CyA at 2–3 mg/kg BW may be the most appropriate option. However, we should adjust the dosage of CyA by therapeutic drug monitoring to avoid complications.

Comparison of tacrolimus with a cyclosporine microemulsion for immunosuppressive therapy in kidney transplantation.

To compare the efficacy and side effects of a cyclosporine microemulsion and tacrolimus in immunosuppressive therapy of renal transplantation. Between March 2003 and June 2005, the patients who had undergone kidney transplantation surgery and who were administered either basiliximab, a cyclosporine microemulsion, mycophenolate mofetil and prednisolone or basiliximab, tacrolimus, mycophenolate mofetil and prednisolone for baseline immunosuppressive therapy were recruited to our study. We evaluated the results of an 18-month follow-up period. The donors were called back weekly for a follow-up in the first month, fortnightly in the second month and then monthly for 18 months after discharge. A total of 41 patients were included in the study. The patients were evaluated as for demographic characteristics, acute rejection, cardiovascular and metabolic side effects, graft function, infections, hirsutism, gingival hyperplasia, cosmetic side effects, nephrotoxicity, drug changes and the survival rates. There were no significant differences among the patients with regard to age, sex, donor type, dialysis periods, preoperative and postoperative systolic blood pressures, creatinine levels, hepatotoxicity, nephrotoxicity, occurrence of diabetes mellitus and the incidence of infection. The duration of hospitalization was prolonged in the cyclosporine A group. Acute rejection emerged in 5 patients (23.8%) in the tacrolimus group and in 4 patients (20%) in the cyclosporine A group. In the cyclosporin A group, the cholesterol and triglyceride levels were significantly higher than the tacrolimus group. The cosmetic side effects (gingival hyperplasia and hirsutism) as a reason for a change in medication were only observed in the cyclosporin A group, not in the tacrolimus group. A medication change was made in 8 patients in the cyclosporine A group and in 1 patient in the tacrolimus group. No death was observed in either group. Graft loss was observed in only 1 patient in the cyclosporine A group. Regarding the cosmetic side effects and hyperlipidemia, tacrolimus was found to be superior to cyclosporine A. Where hyperlipidemia is considered to be a risk factor for cardiovascular disease, tacrolimus use should be considered as a more acceptable treatment modality. However, the immunosuppressive regimen should be evaluated individually.

The case report of a 31-year-old man with giant cell myocarditis successfully treated with combined immunosuppression and veno-arterial extracorporeal membrane oxygenation for 21 days

Introduction: Giant cell myocarditis (GCM) is a life-threatening condition attributed to a T-cell mediated inflammation of the myocardium. The most common early manifestation is acute heart failure. Recovery of myocardial function can occur with non-standardized combined immunosuppression therapy, hemodynamic support, and management of arrhythmias. Case report description: A 31-year-old man with a history of multiple autoimmune disorders (thyroiditis, ulcerative colitis, hepatitis) developed progressive dyspnoea and was transferred to our hospital with severe biventricular dysfunction (left ventricular ejection fraction –LVEF- of 10%) and cardiogenic shock unresponsive to pharmacological treatment 3 days after the onset of symptoms. Mechanically assisted ventilation, intraaortic counterpulsation (IABP) and veno-arterial extracorporeal membrane oxygenation (ECMO) were promptly instituted, and a right ventricle endomyocardial biopsy was performed, which provided the histologic diagnosis of GCM. On this basis, combined immunosuppression with tymoglobulin, steroids, and cyclosporine microemulsion was started. The day after the patient was weaned from the ventilator, but during the next days he remained dependent from circulatory supports, thus was screened for heart transplantion (HTx). After two weeks on IABP and ECMO, LVEF was still 10%, and urgent HTx was requested. No suitable donor heart was offered, and within a few more days a significant recovery of myocardial function was observed, with LVEF increasing up to 50% after 21 days from the initiation of mechanical support and 20 days of immunosuppression. IABP and ECMO were removed on day 21, and after additional 11 days the patient was discharged on cyclosporine and prednisone. One week after discharge, cardiac magnetic resonance (CMR) showed a LVEF 60% with diffuse areas of late gadolinium enhancement. Long term maintenance immunosuppression and surveillance with CMR have been planned. Discussion: Cardiac function may recover completely in GCM, but circulatory support is essential for maintaining hemodynamics and oxygenation, since immunosuppression may require days or weeks to allow resolution of myocardial damage and transplant-free survival. Conclusions: Although GCM is mostly reported to benefit from immunosuppression, no specific recommendations regarding drug combination, dosage and duration are available. In the unusual setting of GCM in a patient with multiorgan manifestations of autoimmunity, long term treatment with a drug combination with a well-known safety and toxicity profile, such as cyclosporine and low-dose prednisone, may be a reasonable choice.

Treatment of Severe Atopic Dermatitis with Cyclosporine: A Review of Eight Patients

AbstractAtopic dermatitis is most frequently well controlled with topical therapeutic agents, but based on several studies, 10-20% of patients need systemic therapy. The most common systemic treatment for atopic dermatitis in everyday practice includes systemic corticosteroids, although there are insufficient valid data to support this. Cyclosporine is the treatment of choice for severe atopic dermatitis resistant to other commonly used treatment options, since its favorable therapeutic risk/benefit ratio is well documented in randomized placebo controlled trials, and also in uncontrolled trials. However, approximately 10% of patients with atopic dermatitis with indication for cyclosporine treatment are actually treated with this modality in Serbia, and there are no published case series on its use in this region so far. In this article, we evaluated the treatment efficacy and safety of cyclosporine microemulsion in patients with severe atopic dermatitis hospitalized at the Military Medical Academy in Belgrade from 2009 to 2012. This restrospective analysis included patients with severe forms of atopic dermatitis treated at the Department of Dermatology of the Military Medical Academy from 2009 - 2012. The hospital database was used to retrieve patients’ medical records. Approximately 200 patients were treated for atopic dermatitis and 20 patients were admitted to the hospital, 17 due to severe forms of disease. In total, 8 of 17 (47.05%) hospitalized patients with severe forms or erythroderma due to atopic dermatitis were treated with cyclosporine microemulsion with an initial dose of 4-5 mg/kg. Laboratory tests were done before treatment, 7 days later, and/or at the end of hospitalization. Therapeutic efficacy was evaluated based on the percentage of reduction of skin lesions from baseline to the end of hospital treatment (early efficacy), and at the end of follow-up (late efficacy). Duration of therapy, adverse events, treatment efficacy and reasons for treatment cessation were recorded during the follow-up period. There were five male and 3 female patients, with an average age of 36.8 years (15 - 60 years). Previous treatment modalities in all patients included emollients, topical and systemic corticosteroids and PUVA therapy. The average dose of cyclosporine was 4.5±0,5 mg/kg. Median reduction of skin lesions at discharge was 60%. There was no need for further hospitalization after an average of 10±3.2 days. Mean duration of treatment was 16 months (3 - 24), with an average reduction of skin lesions of 75% during follow-up. Arterial blood pressure increased in 3/8 (37.5%) patients, regardless of their age, with and average increase of systolic blood pressure of 11.9±11.6 mm Hg (median 7.5, 0-30 mm Hg) and diastolic blood pressure of 5.6±12.9 mm Hg (median 0, -10-20). Mean increase in urea concentration was 0.3 mmol/L (11.8%) and creatinine increased only in three patients by 4.2% (median increase 4 mmol/L). Hypertension was found in three patients during follow-up, and there were no other adverse events. In conclusion, based on previous studies and this small case series of hospitalized patients with severe forms of atopic dermatitis including erythroderma, cyclosporine can be regarded as a safe and effective treatment modality and it can be recommended as first line therapy in severe forms of atopic dermatitis refractory to topical therapy and phototherapy. Long term therapy, however, should be avoided and a maximum 1-2 year therapy is recommended.

Cardiac Allograft Vasculopathy Compared by Intravascular Ultrasound Sonography: Everolimus to Mycophenolate Mofetil—One Single-Center Experience

Cardiac allograft vasculopathy (CAV) remains one of the leading causes of late graft failure and death. Cyclosporine microemulsion Neoral (CsA) had been used in heart transplantation (HTx) recipients. Meanwhile, Everolimus (EVL; Certican, Norvatis Pharmaceuticals; Basel, Switzerland) or mycophenolate mofetil (MMF) have been combined with CsA for maintenance treatment. We compared atherosclerosis in HTx patients showing CAV by intravascular ultrasound (IVUS) in two groups: the CE who received CsA, EVL, and steroid versus the CM group, who received CsA, MMF, and steroid. Materials and MethodsWe explored IVUS parameters such as plaque thickness (PT), lumen circumference (LC), media adventitial circumference, lumen diameter (LD), and media adventitial diameter to characterize the atherosclerosis among CE versus CM groups. ResultsIn this study, both the CE and CM groups showed increased plaque thickening in the first year posttransplantation (P < .05). However, MMF significantly reduced LC and LD (P < .05) Upon multivariate linear regression analysis, the CE group seemed to show less effect on the maximal difference in PT between 2 and 12 months after adjusting for age at transplantation and gender (P < .05). There was no acute clinical adverse event of CAV reported in either both group during the follow-up. The atherosclerosis of CAV revealed by LC, LDmax, and LDmin was significantly less among patients treated with CE than CM. ConclusionThese results suggested that everolimus-treated patients showed benefits compared with MMF-treated subjects as extrapolated from these IVUS data.

Efficacy of Anti-Interleukin-2 Receptor Antibody (Daclizumab) in Reducing the Incidence of Acute Rejection After Renal Transplantation

BackgroundAcute rejection remains a major problem in renal transplantation and represents one of the most important causes of chronic allograft dysfunction and late graft loss. Daclizumab is a genetically engineered human IgG1 monoclonal antibody that binds specifically to the α chain of the interleukin-2 receptor, and may thus reduce the risk of rejection after renal transplantation.ObjectivesThe aim of this study was to examine the effect of daclizumab induction therapy combined with a triple immunosuppressive protocol including prednisolone,cyclosporine microemulsion (CsA), and mycophenolate mofetil (MMF), in reducing the incidence of acute rejection in recipients of living unrelated donor kidneys.Patients and MethodsIn this historical cohort study, 43 adult recipients of their first kidney allograft received daclizumab (three 1 mg/kg doses administered every 2 weeks) with triple immunosuppressive therapy (steroids, CsA, and MMF). This group was compared to 43 first-time graft recipients who received maintenance triple immunosuppressive therapy comprising steroids, CsA, and MMF. The end point was the incidence of biopsy confirmed acute rejection within 6 months after transplantation.ResultsAt 6 months, 5 (11.6%) of the patients in the daclizumab group had biopsy-proven rejections, as compared to 14 (32.5%) in the control group (P = 0.017). The sex and the age of recipients had no impact on the incidence of acute rejection episodes in the two groups.ConclusionsAdding interleukin-2 receptor antibody (daclizumab) to maintenance triple immunosuppressive therapy (prednisolone, CsA, and MMF) reduces the incidence of acute rejection episodes at 6 months in first-time transplant recipients of living unrelated donor.

Cyclosporine Microemulsion Formulation (Sigmasporin Microral) Effect as First-Line Immunosuppressant on Renal Functions at 3 Years

BackgroundCyclosporine (CsA) remains a mainstay of immunosuppressive maintenance regimens in developing countries, but its effects on long-term kidney allograft survival are still unclear. Our aim was to assess a generic microemulsion CsA (Sigmasporin) for long-term impact on graft function and patient survival among stable renal transplant patients. MethodsOver a 36-month period, patients with transplantations from >6 months earlier were maintained on CsA doses of 2–8 mg/kg/d to keep C2 within the recommended therapeutic range. We assessed 25 efficacy and tolerability parameters of scheduled intervals. ResultsTwenty-seven patients (9 female, 18 male) from 6 centers in 4 Middle-Eastern countries were enrolled between 2004 and 2009. Their average age was 35.1 ± 9.8 years, body mass index ranged from 15.7 to 41.2 kg/m2, and average time from transplantation was 2.2 ± 1.6 years. Within the 36-month observation period the CsA dose was reduced by 17.3% from 2.89 ± 0.88 mg/kg/d to achieve C2 levels of 600–1000 ng/mL. After 36 months the glomerular filtration rate declined by 8.2% from an overall baseline mean of 72.7 ± 23.5 mL/min/1.73 m2. It improved in 11.1% of patients and remained unchanged in 44.4%. No new cases of hypertension or diabetes mellitus were reported, and there was 1 case of borderline hyperlipidemia. Graft functions were stable, apart from 2 incidences of CsA nephrotoxicity. Both graft and patient 3-year survival rates were 100%. ConclusionsOn a 3-year basis, Sigmasporin Microral was effective to maintain stable renal functions in kidney transplant patients, with safety and tolerability profiles similar to those reported in the international literature.

Autoimmune Hepatitis Type 2 in a Child With IPEX Syndrome

Autoimmune Hepatitis Type 2 in a Child With IPEX Syndrome